Darwin continues by explaining that "two classes of facts" about the subject of hybridism "have generally been confounded together; namely, the sterility of two species when first crossed, and the sterility of the hybrids produced from them." On the first of these, the sterility, or, inversely, the fertility of two species when crossed, Darwin quotes other researchers of his time and comes to the conclusion that "neither sterility nor fertility affords any clear distinction between species and varieties." In other words, there are some cases in which plants and animals considered to be of different species are able to interbreed, and there are also cases in which those that are merely varieties of the same species are not fertile when crossed. This underscores his earlier point that there is not an exact definition of what constitutes a species.

On the second of these topics, the sterility of the hybrids themselves, Darwin notes that many experiments have shown that hybrid plants are generally less fertile than their parents, but that he believes "that in all these experiments the fertility has been diminished by an independent cause, namely, from close interbreeding" of the hybrids with each other. In fact, he notes, experiments using artificially fertilized hybrid plants have shown an increase in fertility, and it seems that hybrids can actually be more fertile than their parents.

Following these explanations, Darwin comes back to the question of whether sterility is endowed for the purpose of separating species, or whether it is incidental. He repeats that he thinks it is incidental and explains why through a series of questions: "For why should the sterility be so extremely different in degree, when various species are crossed, all of which we must suppose it would be equally important to keep from blending together? Why should the degree of sterility be innately variable in the individuals of the same species?" and so on. He concludes from these questions that "the sterility both of first crosses and of hybrids is simply incidental or dependent on unknown differences, chiefly in the reproductive systems, of the species which are crossed."

Steve Jones, in his chapter on hybridism in Darwin's Ghost, builds on this idea. He writes about modern views on hybridism. It is now possible, through biotechnology, to hybridize virtually any two (or more) species in nearly any way. One of the earliest foods to be modified was the tomato. The tomato has been so heavily modified that Jones questions whether the kind now available in supermarkets is really even the same species as before.

Jones also questions the quality of safeguards put in place to protect consumers of genetically modified foods, as "biotechnology, with its twenty-first-century powers, has an eighteenth-century view of what species are." This eighteenth-century view is that "each species represents a Platonic ideal unable to exchange genes with others." As a result of this view, a "protein that has been proved harmless to man moved to a foreign plant used as food does not even have to be tested in its new home." This is mistake that "takes no account of the notion of species as interacting groups of genes," in which the effects of specific genes depend on the context of other genes present in the species. For instance, Jones writes, some hybrid fish suffer from combinations of genes that cause them to develop cancers that their parent species do not.

Jones sees biotechnology as risky even with testing of every new hybrid, though. Since all species were once varieties, the genes put into a species can actually spread to other species, and sometimes do. "Already," he writes, "genes for herbicide resistance put into oilseed rape have seeped into wild mustards and radishes." He ends his chapter with another statement of the risks of genetic engineering: "Those who cast down the barriers to hybridism will soon be reminded of what evolution can do; and the very fact of [species] permeability is testimony of their origin in descent through modification."